Evaluation of Placement Techniques for DNA Probe Array Layout

Abstract

DNA probe arrays have emerged as a core genomic technology that enables cost-effective gene expression monitoring, mutation detection, single nucleotide polymorphism analysis and other genomic analyses. DNA chips are manufactured through a highly scalable process, Very Large-Scale Immobilized Polymer Synthesis (VL-SIPS), that combines photolithographic technologies adapted from the semiconductor industry with combinatorial chemistry. Commercially available DNA chips contain more than a half million probes and are expected to exceed one hundred million probes in the next generation. This paper is one of the first attempts to apply VLSI CAD methods to the problem of probe placement in DNA chips, where the main objective is to minimize total border cost (i.e., the number of nucleotide mismatches between adjacent sites). We make the following contributions. First, we propose several partitioning-based algorithms for DNA probe placement that improve solution quality by over 4% compared to best previously known methods. Second, we give a simple in-place probe reembedding algorithm with solution quality better than previous chessboard and batched greedy algorithms. Third, we experimentally evaluate scalability and suboptimality of existing and newly proposed probe placement algorithms. Interestingly, we find that DNA placement algorithms appear to have better suboptimality properties than those recently reported for VLSI placement algorithms.